101 - Phase II Prospective Trial of Image-Guided Cognitive-Sparing Brain Radiosurgery (COG-SRS) with a Connectivity Approach: The Future of Functional Preservation
Presenter(s)
A. C. Puett1, R. Karunamuni1, G. G. Y. Kim1, A. B. Hopper1, J. S. Kohli2, N. Menendez1, A. Reyes1, K. R. Tringale1, V. Moiseenko1, P. Sanghvi1, C. McDonald1,2, and J. A. Hattangadi-Gluth1; 1Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 2Department of Psychiatry, University of California San Diego, La Jolla, CA
Purpose/Objective(s): SRS is standard of care for many malignant and benign intracranial lesions. However, ablative radiation doses injure deep white matter tracts (WMT) and hippocampi (HC), with downstream functional decline. Phase III trials demonstrate significant cognitive decline in up to 64% of patients after standard SRS. We performed the first evidence-based, prospective trial of cognitive-sparing brain SRS (COG-SRS), with a primary endpoint of functional preservation.
Materials/Methods: On this single institution phase II trial, high-resolution volumetric MRI, diffusion tensor tractography, and robust automated processing based on a connectome approach to brain function parcellated 23 WMT and the HC for incorporation into the treatment plan, with dose constraints to these eloquent regions based on our prior NTCP studies (single fraction Dmax WMT=12Gy, HC=8.4Gy, with 3 and 5 fraction equivalent doses). Measurements of fractional anisotropy (FA) and mean diffusivity (MD) on diffusion MRI were longitudinally analyzed as biomarkers of WMT injury. QOL assessments and comprehensive neuropsychological testing of verbal memory, language, executive functioning, attention/processing, and fine motor control were performed prior to and 3 months post SRS using well-validated tests. Impairment rate was defined as the percentage of patients whose cognitive test performance was at least 1 standard deviation below validated population norms. Primary outcome of functional preservation was defined as no significant decline in mean test scores, adjusted for age and sex, from pre- to post-SRS using paired sample t-tests.
Results: 84 patients (77 with brain metastases, totaling 182 lesions; 3 with meningiomas; 4 with AVMs) with median age of 61 years were treated with COG-SRS, with a median follow up of 28 months. Cognitive sparing dose constraints to all eloquent structures subserving each cognitive domain were achieved in 78% of cases, while maintaining target coverage and plan quality indices. Local control for treated brain metastases was 98% at 12 months. FA and MD biomarkers showed no significant longitudinal WMT injury within the selected tracts. The mean cognitive impairment rate across all tests was 26% at baseline and 25% after SRS, with no significant change. Mean T-scores revealed no significant decline in cognitive performance or QOL from baseline to 3 months post SRS for any test (all p>0.1), with improvement observed on tests of verbal fluency (COWAT, p=0.02) and word retrieval (BNT, p=0.01).
Conclusion: Image-guided cognitive-sparing brain SRS with a connectivity framework leads to robust preservation of cognitive/fine motor function and QOL for both malignant and benign disease on this prospective trial. Utilizing standard MRI sequences and highly automated robust processing, COG-SRS is widely applicable and thus a major advance in brain radiosurgery.